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1.  Role of presynaptic metabotropic glutamate receptors in the induction of long-term synaptic plasticity of vesicular release 
Neuropharmacology  2012;66:31-39.
While postsynaptic ionotropic and metabotropic glutamate receptors have received the lions share of attention in studies of long-term activity-dependent synaptic plasticity, it is becoming clear that presynaptic metabotropic glutamate receptors play critical roles in both short-term and long-term plasticity of vesicular transmitter release, and that they act both at the level of voltage-dependent calcium channels and directly on proteins of the vesicular release machinery. Activation of G protein-coupled receptors can transiently inhibit vesicular release through the release of Gβγ which binds to both voltage-dependent calcium channels to reduce calcium influx, and directly to the C-terminus region of the SNARE protein SNAP-25. Our recent work has revealed that the binding of Gβγ to SNAP-25 is necessary, but not sufficient, to elicit long-term depression (LTD) of vesicular glutamate release, and that the concomitant release of Gαi and the second messenger nitric oxide are also necessary steps in the presynaptic LTD cascade. Here, we review the current state of knowledge of the molecular steps mediating short-term and long-term plasticity of vesicular release at glutamatergic synapses, and the many gaps that remain to be addressed.
PMCID: PMC3432151  PMID: 22626985
Group II metabotropic glutamate receptors; G protein-coupled receptors; Giα; Gβγ; long-term synaptic depression; SNAP-25; SNARE protein; synaptic plasticity; vesicular release
2.  Spotlight on the active zone 
Cellular Logistics  2011;1(3):84-85.
PMCID: PMC3173654  PMID: 21922071
3.  A parallel cholinergic brainstem pathway for enhancing locomotor drive 
Nature neuroscience  2010;13(6):731-738.
The brainstem locomotor system is believed to be organized serially from the mesencephalic locomotor region (MLR) to reticulospinal neurons, which in turn, project to locomotor neurons in the spinal cord. In contrast, we now identify in lampreys, brainstem muscarinoceptive neurons receiving parallel inputs from the MLR and projecting back to reticulospinal cells to amplify and extend durations of locomotor output. These cells respond to muscarine with extended periods of excitation, receive direct muscarinic excitation from the MLR, and project glutamatergic excitation to reticulospinal neurons. Targeted block of muscarine receptors over these neurons profoundly reduces MLR-induced excitation of reticulospinal neurons and markedly slows MLR-evoked locomotion. Their presence forces us to rethink the organization of supraspinal locomotor control, to include a sustained feedforward loop that boosts locomotor output.
PMCID: PMC2881475  PMID: 20473293
4.  New Perspectives on the Dialogue between Brains and Machines 
Brain-machine interfaces (BMIs) are mostly investigated as a means to provide paralyzed people with new communication channels with the external world. However, the communication between brain and artificial devices also offers a unique opportunity to study the dynamical properties of neural systems. This review focuses on bidirectional interfaces, which operate in two ways by translating neural signals into input commands for the device and the output of the device into neural stimuli. We discuss how bidirectional BMIs help investigating neural information processing and how neural dynamics may participate in the control of external devices. In this respect, a bidirectional BMI can be regarded as a fancy combination of neural recording and stimulation apparatus, connected via an artificial body. The artificial body can be designed in virtually infinite ways in order to observe different aspects of neural dynamics and to approximate desired control policies.
PMCID: PMC2920523  PMID: 20589094
brain-machine interface; dynamical system; dynamical dimension; neural plasticity; lamprey
5.  Presynaptic G protein-coupled receptors dynamically modify vesicle fusion, synaptic cleft glutamate concentrations and motor behavior 
Understanding how neuromodulators regulate behavior requires investigating their effects on functional neural systems, but also their underlying cellular mechanisms. Utilizing extensively characterized lamprey motor circuits, and the unique access to reticulospinal presynaptic terminals in the intact spinal cord that initiate these behaviours, we have investigated effects of presynaptic G protein-coupled receptors on locomotion from the systems level, to the molecular control of vesicle fusion. 5-HT inhibits neurotransmitter release via a Gβγ interaction with the SNARE complex that promotes kiss-and-run vesicle fusion. In the lamprey spinal cord we demonstrate that while presynaptic 5-HT receptors inhibit evoked neurotransmitter release from reticulospinal command neurons, their activation does not abolish locomotion, but rather modulates locomotor rhythms. Liberation of presynaptic Gβγ causes substantial inhibition of AMPA receptor-mediated synaptic responses, but leaves NMDA receptor-mediated components of neurotransmission largely intact. Because Gβγ binding to the SNARE complex is displaced by Ca2+-synaptotagmin binding, 5-HT-mediated inhibition displays Ca2+ sensitivity. We show that as Ca2+ accumulates presynaptically during physiological bouts of activity, 5-HT/Gβγ-mediated presynaptic inhibition is relieved leading to a frequency-dependent increase in synaptic concentrations of glutamate. This frequency dependent phenomenon mirrors a shift in the vesicle fusion mode and a recovery of AMPA receptor-mediated EPSCs from inhibition without a modification of NMDA receptor EPSCs. We conclude that activation of presynaptic 5-HT GPCRs state-dependently alters vesicle fusion properties to shift the weight of NMDA vs AMPA receptor-mediated responses at excitatory synapses. We have therefore identified a novel mechanism in which modification of vesicle fusion modes may profoundly alter locomotor behaviour.
PMCID: PMC2756137  PMID: 19692597
fictive locomotion; kiss-and-run; G protein-coupled receptors; serotonin; presynaptic; Gβγ
6.  Brain-Machine Interactions for Assessing the Dynamics of Neural Systems 
A critical advance for brain–machine interfaces is the establishment of bi-directional communications between the nervous system and external devices. However, the signals generated by a population of neurons are expected to depend in a complex way upon poorly understood neural dynamics. We report a new technique for the identification of the dynamics of a neural population engaged in a bi-directional interaction with an external device. We placed in vitro preparations from the lamprey brainstem in a closed-loop interaction with simulated dynamical devices having different numbers of degrees of freedom. We used the observed behaviors of this composite system to assess how many independent parameters − or state variables − determine at each instant the output of the neural system. This information, known as the dynamical dimension of a system, allows predicting future behaviors based on the present state and the future inputs. A relevant novelty in this approach is the possibility to assess a computational property – the dynamical dimension of a neuronal population – through a simple experimental technique based on the bi-directional interaction with simulated dynamical devices. We present a set of results that demonstrate the possibility of obtaining stable and reliable measures of the dynamical dimension of a neural preparation.
PMCID: PMC2679156  PMID: 19430593
lamprey brainstem; closed-loop system; dynamical dimension; simulated dynamical device

Results 1-6 (6)